title: Novel region discovery method for Infinium 450K DNA methylation data reveals changes associated with aging in muscle and neuronal pathways.
abstract: We describe a methodology for detecting differentially methylated regions (DMRs) and variably methylated regions (VMRs), in data from Infinium 450K arrays that are very widely used in epigenetic studies. Region detection is more specific than single CpG analysis as it increases the extent of common findings between studies, and is more powerful as it reduces the multiple testing problem inherent in epigenetic whole-genome association studies (EWAS). In addition, results driven by single erroneous probes are removed. We have used multiple publicly available Infinium 450K data sets to generate a consensus list of DMRs for age, supporting the hypothesis that aging is associated with specific epigenetic modifications. The consensus aging DMRs are significantly enriched for muscle biogenesis pathways. We find a massive increase in VMRs with age and in regions of the genome associated with open chromatin and neurotransmission. Old age VMRs are significantly enriched for neurotransmission pathways. EWAS studies should investigate the role of this interindividual variation in DNA methylation, in the age-associated diseases of sarcopenia and dementia.
authors.affiliation: Singapore Institute for Clinical Sciences, Agency for Science Technology and Research (A*STAR), Brenner Centre for Molecular Medicine, 30 Medical Drive, Singapore, 117609, Singapore.
authors.forename: Mei-Lyn
authors.initials: ML
authors.lastname: Ong
authors.forename: Joanna Dawn
authors.initials: JD
authors.lastname: Holbrook
mesh_terms: D000293:Adolescent; D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002843:Chromatin / Q000378:metabolism; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D015342:DNA Probes / Q000378:metabolism; D003850:Deoxyribonuclease I / Q000378:metabolism; D005260:Female; D005796:Genes; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009132:Muscles / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D040641:Quantitative Trait Loci / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics*
chemical_list: D002843:Chromatin; D015342:DNA Probes; D003850:Deoxyribonuclease I
keywords: EWAS; Infinium; aging; epigenetics; methylation; sarcopenia